Proteomic analysis reveals novel binding partners of dysbindin, a schizophrenia-related protein

Takao Hikita, Shinichiro Taya, Yasutaka Fujino, Setsuko Taneichi-Kuroda, Kanae Ohta, Daisuke Tsuboi, Tomoyasu Shinoda, Keisuke Kuroda, Yusuke Funahashi, Junko Uraguchi-Asaki, Ryota Hashimoto, Kozo Kaibuchi

Research output: Contribution to journalArticlepeer-review

30 Citations (Scopus)


Schizophrenia is a complex mental disorder with fairly high level of heritability. Dystrobrevin binding protein 1, a gene encoding dysbindin protein, is a susceptibility gene for schizophrenia that was identified by family-based association analysis. Recent studies revealed that dysbindin is involved in the exocytosis and/or formation of synaptic vesicles. However, the molecular function of dysbindin in synaptic transmission is largely unknown. To investigate the signaling pathway in which dysbindin is involved, we isolated dysbindin-interacting molecules from rat brain lysate by combining ammonium sulfate precipitation and dysbindin-affinity column chromatography, and identified dysbindin-interacting proteins by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry and liquid chromatography-tandem mass spectrometry. Proteins involved in protein localization process, including Munc18-1, were identified as dysbindin-interacting proteins. Munc18-1 was co-immunoprecipitated with dysbindin from rat brain lysate, and directly interacted with dysbindin in vitro. In primary cultured rat hippocampal neurons, a part of dysbindin was co-localized with Munc18-1 at pre-synaptic terminals. Our result suggests a role for dysbindin in synaptic vesicle exocytosis via interaction with Munc18-1.

Original languageEnglish
Pages (from-to)1567-1574
Number of pages8
JournalJournal of Neurochemistry
Issue number5
Publication statusPublished - Sept 2009
Externally publishedYes


  • Dysbindin
  • Munc18-1
  • Proteomics
  • Schizophrenia
  • Susceptibility gene

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience


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